Cerebrospinal fluid detection of interleukin-1ß in phase of remission predicts disease progression in multiple sclerosis.

BACKGROUND: Absence of clinical and radiological activity in relapsing-remitting multiple sclerosis (RRMS) is perceived as disease remission. We explored the role of persisting inflammation during remission in disease evolution. METHODS: Cerebrospinal fluid (CSF) levels of interleukin 1ß (IL-1ß), a major proinflammatory cytokine, were measured in 170 RRMS patients at the time of clinical and radiological remission. These patients were then followed up for at least 4 years, and clinical, magnetic resonance imaging (MRI) and optical coherence tomography (OCT) measures of disease progression were recorded. RESULTS: Median follow-up of RRMS patients was 5 years. Detection of CSF IL-1ß levels at the time of remission did not predict earlier relapse or new MRI lesion formation. Detection of IL-1ß in the CSF was instead associated with higher progression index (PI) and Multiple Sclerosis Severity Scale (MSSS) scores at follow-up, and the number of patients with sustained Expanded Disability Status Scale (EDSS) or Multiple Sclerosis Functional Composite worsening at follow-up was higher in individuals with detectable levels of IL-1ß. Patients with undetectable IL-1ß in the CSF had significantly lower PI and MSSS scores and a higher probability of having a benign MS phenotype. Furthermore, patients with undetectable CSF levels of IL-1ß had less retinal nerve fiber layer thickness and macular volume alterations visualized by OCT compared to patients with detectable IL-1ß. CONCLUSIONS: Our results suggest that persistence of a proinflammatory environment in RRMS patients during clinical and radiological remission influences midterm disease progression. Detection of IL-1ß in the CSF at the time of remission appears to be a potential negative prognostic factor in RRMS patients.

Ultrasound-guided pulsed radiofrequency of the saphenous nerve for knee osteoarthritis pain: a pilot randomized trial.

Aim: Knee osteoarthritis is a degenerative disease complicated by pain and functional limitation. Newer pain-relieving interventions include pulsed radiofrequency (PRF), but studies on its efficacy have limitations including lack of control group and retrospective design that prevent sound conclusions. Materials & methods: We conducted a blind prospective randomized sham-controlled crossover pilot trial according to the CONSORT guidelines, to evaluate the efficacy of ultrasound-guided saphenous nerve PRF in gonarthritis pain. Results: Sixteen patients completed the study. Pain and function significantly improved after real PRF (numerical rating scale mean difference = 3.31), which was superior to sham PRF over time for pain (3 months) and function (6 months). Conclusion: PRF of the saphenous nerve is an alternative to relieve pain in gonarthritis. Our results provide data to support a sample size calculation for future trials. Clinical trial registration: NCT04454710.

Lay abstract Aim: Knee osteoarthritis is a degenerative disease associated with severe pain and functional limitation. While treatment options exist to manage knee arthritis symptoms, few have achieved very good results. Newer pain-relieving treatments include pulsed radiofrequency (PRF), where electrical pulses are delivered to the painful nerves to change the way electrical signals are transmitted and reduce pain, but studies on its efficacy have limitations that prevent sound conclusions. Materials & methods: We conducted a study specifically designed to reveal efficacy of PRF over a sham (fake) treatment in patients affected by severe knee arthritis by targeting one single nerve involved in transmitting pain signals from the knee. Results: Pain and function significantly improved after real PRF, which was superior to sham PRF over time for pain (3 months) and function (6 months). Conclusion: PRF of the saphenous nerve is an alternative to relieve pain in knee arthritis.

Efficacy and tolerability of orally administered tramadol/dexketoprofen fixed-dose combination compared to diclofenac/thiocolchicoside in acute low back pain: experience from an Italian, single-centre, observational study.

OBJECTIVES: To compare the analgesic efficacy and tolerability of tramadol/dexketoprofen 75/25 mg (TRAM/DKP) versus diclofenac/thiocolchicoside 75/4 mg (DIC/THIO) in patients with moderate-to-severe acute low back pain (LBP). METHODS: Single-centre, observational study in 82 adult outpatients with LBP due to disc herniation (≥4 Numerical Rating scale, NRS) who received either oral TRAM/DKP (n = 44) or intramuscular DIC/THIO (n = 38), both given every 12 h for 5 days. The primary endpoint was the change from baseline in pain intensity (PI) at pre-specified post-dose time points (t day1, t day3, t day7) and compared between the two treatments. Additional endpoints, all evaluated at day 7, included: the sum of PI difference (SPID), percentage of responders in terms of PI reduction versus baseline and change from baseline in Douleur Neuropathique (DN4) score. Tolerability and safety were also assessed. RESULTS: Both treatment groups were comparable for demographic characteristics and comorbidities. Over the 5-day treatment period and up to day 7, compared to DIC/THIO, TRAM/DKP provided a significantly greater and sustained analgesia at day 3 and day 7 (p < .0001), with a higher proportion of responders at each time point [75% versus 71.1% (p = 0.687) at day 1, 93.2% versus 73.7% at day 3 (p = .016) and 95.5% versus 71.1% at day 7 (p = .003)], higher values of SPID (770.9 ± 23.5 vs. 507.1 ± 22.6; p < .0001) and significantly greater reduction in DN4 score [-62.7 ± 25.6 vs. -39.7 ± 31.2 (p < .0001)]. Both treatments were well tolerated. CONCLUSIONS: Orally administered TRAM/DKP 75/25 mg can be a valuable and effective option in patients with acute LBP.

Endoscopic Neuromodulation of Suprascapular Nerve in Chronic Shoulder Pain: A Case Report.

Shoulder pain is very frequent, especially in middle-aged male adults. Its treatment may be very problematic, mainly in patients who cannot rest and stop their work. At present, it is treated with analgesics, physiotherapy, infiltration of corticosteroids, and/or radiofrequency neuromodulation of the suprascapular nerve. This may be effective but not easy to do. Its efficacy is limited in time, especially because the approach to the nerve trunk may be problematic for its anatomical nature. Ultrasonography has helped, but it is not always completely helpful, due to the small dimension and the complexity of the anatomical structure. In this case report, we describe a more helpful approach to the nerve trunk using an endoscopic technique. The results are very promising. However, larger studies would be necessary to make clear its usefulness.

Endoscopic radiofrequency facet joint treatment in patients with low back pain: technique and long-term results. A prospective cohort study.

AIMS: The aim of the study was to evaluate the efficacy of endoscopic rhizotomy (ER) for denervation of lumbar facet joints in patients with chronic low back pain (LBP) due to facet joint syndrome (FJS). METHODS: A total of 50 consecutive patients suffering from chronic LBP due to facet joints were screened to be treated with ER. The patients participating in the study had a 2-year follow up. Numeric Rating Scale (NRS) and Oswestry Disability Index (ODI) were assessed in the preoperative and postoperative period. To evaluate secondary endpoints, patients were divided into groups. One group included the patients previously treated with percutaneous radiofrequency (RF). The other group comprised patients at their first interventional treatment. We also compared patients dividing them by age and by number of joints treated, trying to elucidate if these parameters could be predictive of effectiveness of the procedure. RESULTS: All patients had a reduction in NRS and an improvement in ODI. NRS was reduced significantly after 1 month and remained the same until the end of the study. ODI was significantly improved from T1 (1 month after surgery) up to T7 (end of the study). The improvements did not differ whether already treated with percutaneous rhizotomy or not. Patients less than 60 years or with 1-2 joints treated had better improvement compared with the others. CONCLUSION: The results obtained demonstrate that ER for denervation of the facet joint is an effective treatment in patients with chronic LBP, with consistent and stable results at 2-year follow up. The technique has a rapid learning curve and no major complications occurred. Moreover, the previous percutaneous RF treatment had no influence on the results obtained with endoscopic technique. There is evidence that best results are obtained in younger patients and/or in patients with 1-2 joints treated. LAY SUMMARY: Low-back pain has facet joints inflammation or degeneration as pain generator in 20-40% of cases. Nervous lesion of the dorsal ramus innervating the facet joints has been shown as an efficacious treatment to obtain good analgesia. Percutaneous techniques have provided short term results for several reasons. This research aimed to see whether endoscopic denervation, which guarantees a more precise approach to anatomical structure, would result in more durable results. The study conducted on 40 patients has made it clear that this approach gives significant analgesia for at least 2 years, which was the time of patient follow up.

Disability and Fatigue Can Be Objectively Measured in Multiple Sclerosis.

BACKGROUND: The available clinical outcome measures of disability in multiple sclerosis are not adequately responsive or sensitive. OBJECTIVE: To investigate the feasibility of inertial sensor-based gait analysis in multiple sclerosis. METHODS: A cross-sectional study of 80 multiple sclerosis patients and 50 healthy controls was performed. Lower-limb kinematics was evaluated by using a commercially available magnetic inertial measurement unit system. Mean and standard deviation of range of motion (mROM, sROM) for each joint of lower limbs were calculated in one minute walking test. A motor performance index (E) defined as the sum of sROMs was proposed. RESULTS: We established two novel observer-independent measures of disability. Hip mROM was extremely sensitive in measuring lower limb motor impairment, being correlated with muscle strength and also altered in patients without clinically detectable disability. On the other hand, E index discriminated patients according to disability, being altered only in patients with moderate and severe disability, regardless of walking speed. It was strongly correlated with fatigue and patient-perceived health status. CONCLUSIONS: Inertial sensor-based gait analysis is feasible and can detect clinical and subclinical disability in multiple sclerosis.

Treatment options to reduce disease activity after natalizumab: paradoxical effects of corticosteroids.

AIM: Natalizumab (NTZ) discontinuation leads to multiple sclerosis (MS) recurrence, but represents the only known strategy to limit the risk of progressive multifocal leukoencephalopathy (PML) in JCV seropositive patients. Here, we compared the clinical and imaging features of three groups of patients who discontinued NTZ treatment. METHODS: We treated 25 patients with subcutaneous INFß-1b (INF group), 40 patients with glatiramer acetate (GA group), and 40 patients with GA plus pulse steroid (GA+CS group). RESULTS: Six of 25 patients (24%) of the INF group were relapse-free 6 months after NTZ suspension. In GA group, a significant higher proportion of patients (26 of 40 patients, 65%) were relapse-free (P<0.05). Far from improving the clinical effects of GA in post-NTZ setting, combination of GA+CS was associated with lower relapse-free rate than GA alone (40% vs. 65%, P=0.04). Also on MRI parameters, combination of GA+CS was associated with worse outcome than GA alone, as 22 of 26 subjects (84.6%) had MRI evidence of disease activity 6 months after NTZ discontinuation. CONCLUSION: Corticosteroids should not be used in combination with GA to prevent post-NTZ disease recurrence.